Synthesis, screening and docking of fused pyrano[3,2-d]pyrimidine derivatives as xanthine oxidase inhibitor

Manroopraj Kaur, Amandeep Kaur, Suhani Mankotia, Harbinder Singh, Arshdeep Singh, Jatinder Vir Singh, Manish Kumar Gupta, Sahil Sharma, Kunal Nepali, Preet Mohinder Singh Bedi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In view of developing effective xanthine oxidase (XO) enzyme inhibitors, a series of 100 pyrano[3,2-d]pyrimidine derivatives was synthesized and evaluated for its in vitro XO enzyme inhibition. Structure activity relationship has also been established. Among all the synthesized compounds, 4d, 8d and 9d were found to be the most potent enzyme inhibitors with IC50 values of 8μM, 8.5μM and 7μM, respectively. Compound 9d was further investigated in enzyme kinetic studies and the Lineweaver-Burk plot revealed that the compound 9d was mixed type inhibitor. Molecular properties of the most potent compounds 4d, 8d and 9d, have also been calculated. Docking study was performed to investigate the recognition pattern between xanthine oxidase and the most potent XO inhibitor, 9d. The study suggests that 9d may block the activity of XO sufficiently enough to prevent the substrate from binding to its active site.

Original languageEnglish
Pages (from-to)14-28
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Volume131
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

Fingerprint

Xanthine Oxidase
Screening
Derivatives
Enzyme Inhibitors
Enzyme inhibition
Enzyme kinetics
Enzymes
Structure-Activity Relationship
Inhibitory Concentration 50
Pattern recognition
Catalytic Domain
pyrimidine
Substrates

Keywords

  • Enzyme kinetics
  • Lineweaver-Burk plot
  • Molecular modeling studies
  • Pyrano[3,2-d]pyrimidine
  • Xanthine oxidase enzyme

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis, screening and docking of fused pyrano[3,2-d]pyrimidine derivatives as xanthine oxidase inhibitor. / Kaur, Manroopraj; Kaur, Amandeep; Mankotia, Suhani; Singh, Harbinder; Singh, Arshdeep; Singh, Jatinder Vir; Gupta, Manish Kumar; Sharma, Sahil; Nepali, Kunal; Bedi, Preet Mohinder Singh.

In: European Journal of Medicinal Chemistry, Vol. 131, 01.01.2017, p. 14-28.

Research output: Contribution to journalArticle

Kaur, Manroopraj ; Kaur, Amandeep ; Mankotia, Suhani ; Singh, Harbinder ; Singh, Arshdeep ; Singh, Jatinder Vir ; Gupta, Manish Kumar ; Sharma, Sahil ; Nepali, Kunal ; Bedi, Preet Mohinder Singh. / Synthesis, screening and docking of fused pyrano[3,2-d]pyrimidine derivatives as xanthine oxidase inhibitor. In: European Journal of Medicinal Chemistry. 2017 ; Vol. 131. pp. 14-28.
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